Is hippocampal theta frequency related to individual and sex differences in anxiety-like behaviour? An analysis in male and female Long-Evans rats

Abstract

Hippocampal theta activity is a prominent slow (4–12 Hz) oscillatory activity pattern generated in the mammalian hippocampal formation. Based on evidence that anxiolytic drugs consistently decrease the frequency of hippocampal theta activity in rodents, hippocampal theta has been linked to anxiety states, leading to the influential theta suppression model of anxiolysis. Surprisingly, very few studies have examined whether hippocampal theta frequency relates to individual or sex differences in anxiety-like behaviour. Here, male and female rats were tested on the elevated plus maze (EPM) to quantify levels of defensive, anxiety-like behaviours. Females exhibited higher levels of open arm exploration (open arm entries and open arm time) compared to males, suggestive of reduced anxiety in females. Subsequently, reticular-elicited hippocampal theta activity was characterized in the same rats under deep urethane anesthesia. There was no sex difference in theta frequency over a range of stimulation intensities. Further, there were no significant correlations between behavioural measures of anxiety in the EPM and theta frequency among individual animals. Theta frequency did, however, decrease following systemic administration of the clinically-used anxiolytic agent buspirone (10 mg/kg). Together, these results suggest that theta frequency does not relate to levels of anxiety-like behaviours in the EPM in male and female rats, challenging the predictive validity of hippocampal theta activity as an index of anxiety in rodents.